India accounts for one fourth of the global burden of tuberculosis (TB) including an estimated 20,000-40,000 cases in pregnant women. Epidemiologic studies have shown that TB risk is increased post-partum, probably due to increased detection of disease that developed during pregnancy. Definitive prospective studies have not been done to address this issue. TB is a leading cause of death in women during their reproductive years and places the neonate at risk. Yet, these statements about TB in pregnancy are based on small retrospective studies. As a result, current recommendations concerning diagnosis and management of TB in pregnancy are not evidence-based. HIV infection provides further impetus to strengthen the quality of evidence underlying the guidelines and better characterize TB in pregnancy because more pregnant women will be treated and more neonates exposed to anti-TB drugs. US and Indian investigators at Boston University School of Medicine, Rutgers University, and Jawaharlal Institute of Postgraduate Medical Education & Research propose to build on an existing cohort study funded through the Indo-US Vaccine Action Plan (Regional Prospective Observational Research on TB, RePORT India) to focus on TB in pregnancy. Through RePORT India we project enrollment of 2500 TB cases and 3300 exposed household contacts over 5 years. The cohorts will provide access to sufficient numbers of TB cases in pregnant women, household contacts with latent TB infection (LTBI) that will become pregnant during the follow-up period, and appropriate controls to address the following hypotheses: i) the immunosuppression of pregnancy modulates the diagnostic biomarkers of LTBI, confounding its diagnosis and is associated with host biomarkers indicative of risk of disease; ii) pregnancy increases the risk and severity of TB; iii) poor birth outcomes are more common in pregnant women with TB, and iv) The response to anti-tuberculous drugs is sub-optimal. Specific Aims of this proposal are: 1. To determine the impact of becoming pregnant on diagnostic biomarkers of LTBI and on host biomarkers that may predict risk of progression to TB. 2. To determine the risk of TB in pregnancy and describe the severity of disease, the response to treatment, and pregnancy outcomes. 3.To evaluate the pharmacokinetics of TB drugs during pregnancy and assess exposure of the fetus to them. This research will provide critical data on TB in pregnant women, a long-neglected at-risk population, and provide the foundation for evidence-based recommendations to improve diagnosis of LTBI and treatment of TB disease with attention to minimizing potentially deleterious effects on the fetus.